Background

Dr. John Barrett received his M.B. and B.S. degrees from the Medical College of St. Bartholomew’s Hospital, London in 1968, and his M.D. degree from University of London in 1975. From 1978 to 1988 he was head of the department of hematology at Charing Cross and Westminster Medical School, London, and from 1988 to 1993 he was professor of hematological medicine at the Hammersmith Hospital, London. Dr. Barrett joined the NHLBI in 1993, as the chief of the Bone Marrow Stem Cell Allotransplantation Section of the Hematology Branch. He has received numerous honors for his contributions to hematology and stem cell transplantation including awards from the National Institutes of Health and the National Health Service UK. Dr. Barrett was elected a Fellow of the Royal College of Physicians in 1998. He has authored over 300 original scientific articles, and nearly 150 reviews, editorials, and book chapters. He serves on numerous journal editorial boards and is the Editor in Chief for Cytotherapy. Dr. Barrett is a member of the Royal Society of Medicine, British Society for Haematology, American Society of Hematology, American Society for Blood and Bone Marrow Transplantation (for which he served as President in 2010), and International Society for Cell Therapy, among other organizations.

Research Interests

The Barrett laboratory is interested in improving leukemia outcomes by using immune tricks and technologies associated with stem cell transplantation. Stem cell transplantation offers hope for leukemia patients, many of whom are older and cannot tolerate intense and prolonged sessions of chemotherapy. In addition, disease relapse is also a significant obstacle as the biggest single problem post-transplantation.

One approach for enhancing stem cell therapy involves transplanting components of the donor’s immune system into the patient in addition to the bone marrow stem cells triggering a better graft vs. leukemia (GVL) response in the host. A strong GVL response can eliminate residual disease following transplantation surgery to prevent relapse. While the GVL effect is very powerful, harmful GVH reactions are a particular problem when the donor is only partially-matched with the recipient. Dr. Barrett’s group is exploring ways to prevent the graft vs. host (GVH) reaction to avert tissue damage. Grafts can be made more tolerant by treatment with low doses of a lymphocyte growth factor called interleukin-2 (IL-2), and Dr. Barrett’s group is developing a new partially matched transplant protocol using IL-2 to mitigate otherwise dangerous GVH reactions. Dr. Barrett is also performing clinical research to investigate the ability of mesenchymal stromal cell (MSC) infusions to repair tissues damaged by GVH following transplantation.

As a physician-scientist, Dr. Barrett also leads a basic science program to better understand the nature of the interaction of acute leukemias with the patient’s immune system. An emerging concept from this work is that leukemia cells develop multiple ways to switch off the immune response that might otherwise overwhelm the leukemic process. Understanding these mechanisms of “immune editing” should lead to ways to re-establish immune control of the leukemia by combining standard chemotherapy with immunotherapy to boost patients’ own anti-leukemia defenses and preventing relapse of the leukemia. Furthermore the group plans to develop a comprehensive knowledge of the antigens on leukemia cells that render them targets for immune attack. This is the basis for generating powerful leukemia-specific killer cells that could enhance the GVL response after transplant and eventually extend to the treatment of patients in remission from leukemia to prevent relapse of their disease. The laboratory is already using a similar antigen-refinement strategy to develop anti-virus T-cells from stem cell transplant donors. These cells can target the viruses that normally lie dormant in an individual but can cause problems following transplantation when the subject is in a weakened immune state.

Through this combined translational and clinical strategy, Dr. Barrett’s group is working toward unlocking the tremendous potential that stem cell transplantation therapy holds in curing leukemia and other serious blood and bone marrow disorders.